The proposed research is an extension of our previous studies on the growth and development of the sympathetic nervous system. Using biochemical, pharmacologic and morphologic techniques we have defined the formation of synaptic connections during growth, have found that a bidirectional flow of information across the synapse regulates development, and have begun to define these trans-synaptic molecular message(s) and their trophic effects. The present studies will focus on the molecular mechanisms regulating nerve growth in the brain and peripheral nervous system. More specifically we hope to (a) define the mechanisms by which the central nervous system regulates maturation of neurotransmitter enzymes in sympathetic and spinal motor neurons; (b) further characterize the trans-synaptic messages in sympathetic ganglia; (c) further define the regulation of target innervation by sympathetic nerves; (d) determine how targets govern neuron growth; (e) define development of brain nuclei; (f) use the above information to understand inter-neuronal communication and synaptic plasticity.